DESCRIPTION (adapted from investigator's abstract and/or aims): During the previous funding period, the applicant demonstrated that heme oxygenase is a key enzyme in heme metabolism and purified that enzyme to homogeneity; partially sequenced it; prepared antibodies to it and has begun to use antibodies as a tool to quantify HO levels in many tissues. In this renewal proposal, the applicant proposes to extend his previous studies of HO by; further analysis of the HO protein; improvement of the immunochemical analysis for HO which he has developed; cloning, sequencing and characterizing the structural gene coding for HO starting with a cDNA library; cloning of the 5' cis-acting HO regulatory sequences from a genomic library; analyzing the regulation of HO gene expression at the levels of transcription and translation during physiologically relevant states with particular reference to fetal-adult phenotypes; studying the mechanism whereby zinc (Zn++) prevents the potentiating effect of iron on uroporphyrin accumulation by liver cell cultures; and exploring the effects of clinically relevant drugs, metals, energy substrates and hormones on key enzymes of heme metabolism.